Development of Therapeutic Bispecific Antibodies for Tuft Cell Associated Allergic Disease

Developing T cell-redirecting bispecific antibodies to selectively eliminate tuft cells and break the cycle of Type 2 inflammation in CRSwNP.
Ongoing Allergic & Atopic Diseases Animal Models Biological & Mechanistic Cytokine Signaling Experimental Platforms & Models T Cell Biology Therapeutic Development Translational & Clinical

Funding Year: 2024

Project Overview

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) affects nearly 10 million Americans, causing chronic nasal congestion, inflammation, and loss of smell, yet current treatments offer only temporary relief. Recent research identified tuft cells — rare epithelial cells in the nasal lining — as key drivers of Type 2 inflammation in CRSwNP. This project develops a bispecific antibody, anti-CD300lf/CD3, designed to redirect the body's own CD8+ T cells to recognize and eliminate tuft cells, breaking the inflammatory cycle. Preliminary studies confirm tuft cells can be selectively eliminated in mice, and the lead candidate is a first-in-class therapy with strong IP potential — with humanized antibody optimization and early-stage clinical trials in CRSwNP as the next steps if preclinical results confirm efficacy and safety.

Impact & Innovation

A first-in-class antibody targeting the cellular root of nasal polyp disease.

 

By redirecting CD8+ T cells to eliminate tuft cells — the upstream drivers of Type 2 inflammation in CRSwNP — this project moves beyond symptom management toward durable disease modification, with applicability to tuft cell-driven cancers.

  • Pioneers tuft cell depletion as a therapeutic strategy in CRSwNP, addressing a disease where no therapies currently target the upstream cellular driver of inflammation
  • Generates strong IP potential through a first-in-class anti-CD300lf/CD3 bispecific antibody candidate with broad applicability to tuft cell-associated conditions including small cell lung cancer
  • Advances the Consortium’s From Mechanistic Insight to Translation pillar by moving a novel epithelial cell biology discovery into a structured bispecific antibody development and preclinical validation pipeline
Research Approach

A framework designed for discovery

This project combines tuft cell biology, antibody engineering, and in vivo mouse modeling to develop and validate a T cell-redirecting bispecific antibody that selectively eliminates tuft cells and disrupts Type 2 inflammation in CRSwNP. The work moves from target validation through lead candidate development and preclinical efficacy and safety testing.


Development of anti-CD300lf/CD3 T cell-directed bispecific antibodies (bsAbs) designed to engage the immune system for tuft cell depletion; in vivo testing in mouse models to assess safety, effectiveness, and optimal administration; and preliminary tuft cell elimination studies using CD8+ T cell redirection.


Mouse models of CRSwNP and tuft cell-driven inflammation, in vivo tuft cell depletion datasets confirming selective elimination by CD8+ T cells, and preclinical efficacy and safety datasets for anti-CD300lf/CD3 bispecific antibody candidates.

Validation of tuft cell depletion as a durable therapeutic strategy for CRSwNP and related Type 2 inflammatory diseases, with a translational path toward humanized antibody optimization, IP protection, and early-stage clinical trials in CRSwNP. The approach may also extend to tuft cell-variant small cell lung cancer and other tuft cell-associated conditions.

Investigators & Institutions

Powering the science

Principal Investigator

Craig B. Wilen, MD, PhD, Colton Consortium Member

Associate Professor, Department of Laboratory Medicine, Yale School of Medicine, Yale University

Colton Centers & Institutions

Colton Center for Autoimmunity at Yale University